tbuckley/cabot-search huggingface dataset:
Long-term Survival Benefit From Revascularization Compared With Medical Therapy in Patients With or Without Diabetes Undergoing Myocardial Perfusion Single Photon Emission Computed Tomography
Authors: Keiichiro Kuronuma, Donghee Han, Robert J.H. Miller, Alan Rozanski, Heidi Gransar, Damini Dey, Sean W. Hayes, John D. Friedman, Louise Thomson, Piotr J. Slomka, Daniel S. Berman
Journal: Diabetes Care (2022)

OBJECTIVE To explore the long-term association of survival benefit from early revascularization with the magnitude of ischemia in patients with diabetes compared with those without diabetes using a large observational cohort of patients undergoing single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). RESEARCH DESIGN AND METHODS Of 41,982 patients who underwent stress and rest SPECT-MPI from 1998 to 2017, 8,328 (19.8%) had diabetes. A propensity score was used to match 8,046 patients with diabetes to 8,046 patients without diabetes. Early revascularization was defined as occurring within 90 days after SPECT-MPI. The percentage of myocardial ischemia was assessed from the magnitude of reversible myocardial perfusion defect on SPECT-MPI. RESULTS Over a median 10.3-year follow-up, the annualized mortality rate was higher for the patients with diabetes compared with those without diabetes (4.7 vs. 3.6%; P &amp;lt; 0.001). There were significant interactions between early revascularization and percent myocardial ischemia in patients with and without diabetes (all interaction P values &amp;lt;0.05). After adjusting for confounding variables, survival benefit from early revascularization was observed in patients with diabetes above a threshold of &amp;gt;8.6% ischemia and in patients without diabetes above a threshold of &amp;gt;12.1%. Patients with diabetes receiving insulin had a higher mortality rate (6.2 vs. 4.1%; P &amp;lt; 0.001), but there was no interaction between revascularization and insulin use (interaction P value = 0.405). CONCLUSIONS Patients with diabetes, especially those on insulin treatment, had higher mortality rate compared with patients without diabetes. Early revascularization was associated with a mortality benefit at a lower ischemic threshold in patients with diabetes compared with those without diabetes.
Retraction Note to: MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial–mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma
Authors: Zhenyue He, Jun Yi, Xiaolong Liu, Jing Chen, Siqi Han, Li Jin, Longbang Chen, Haizhu Song
Journal: Molecular Cancer (2022)

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-016-0533-3.
Comparing Kidney Health Outcomes in Children, Adolescents, and Adults With Focal Segmental Glomerulosclerosis
Authors: Debbie S. Gipson, Jonathan P. Troost, Cathie Spino, Samara Attalla, Joshua Tarnoff, Susan Massengill, Richard Lafayette, Virginia Vega-Warner, Sharon Adler, Patrick Gipson, Matthew Elliott, Frederick Kaskel, Damian Fermin, Marva Moxey-Mims, Richard N. Fine, Elizabeth J. Brown, Kimberly Reidy, Katherine Tuttle, Keisha Gibson, Kevin V. Lemley, Larry A. Greenbaum, Meredith A. Atkinson, Sangeeta Hingorani, Tarak Srivastava, Christine B. Sethna, Kevin Meyers, Cheryl Tran, Katherine M. Dell, Chia-shi Wang, Jennifer Lai Yee, Matthew G. Sampson, Rasheed Gbadegesin, J. J. Lin, Tammy Brady, Michelle Rheault, Howard Trachtman
Journal: JAMA Network Open (2022)

Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials.
Aconitate decarboxylase 1 is a mediator of polymicrobial sepsis
Authors: Runliu Wu, Jiao Liu, Nian Wang, Ling Zeng, Chunhua Yu, Feng Chen, Haichao Wang, Timothy R. Billiar, Jianxin Jiang, Daolin Tang, Rui Kang
Journal: Science Translational Medicine (2022)

Sepsis is a challenging clinical syndrome caused by a dysregulated host response to infection. Here, we identified an unexpected proseptic activity of aconitate decarboxylase 1 (ACOD1) in monocytes and macrophages. Previous studies have suggested that ACOD1, also known as immune-responsive gene 1, is an immunometabolic regulator that favors itaconate production to inhibit bacterial lipopolysaccharide-induced innate immunity. We used next-generation sequencing of lipopolysaccharide-activated THP1 cells to demonstrate that ACOD1 accumulation confers a robust proinflammation response by activating a cytokine storm, predominantly through the tumor necrosis factor signaling pathway. We further revealed that the phosphorylation of cyclin-dependent kinase 2 (CDK2) on threonine-160 mediates the activation of mitogen-activated protein kinase 8 through receptor for activated C kinase 1, leading to JUN-dependent transcription of ACOD1 in human and mouse macrophages or monocytes. Genetic deletion of CDK2 or ACOD1 in myeloid cells, or the administration of the CDK inhibitor dinaciclib, protected mice against polymicrobial sepsis and was associated with improved survival and decreased cytokine storm. The expression of the CDK2-ACOD1 axis also correlated with severity of illness in a cohort of 40 patients with bacterial sepsis. Thus, our findings provide evidence for a previously unrecognized function of ACOD1 in innate immunity and suggest it as a potential therapeutic target for the treatment of sepsis.
Analysis of Functional Recovery in Older Adults Discharged to Skilled Nursing Facilities and Then Home
Authors: Sandra Shi, Brianne Olivieri-Mui, Gahee Oh, Ellen McCarthy, Dae Hyun Kim
Journal: JAMA Network Open (2022)

Although many older adults are discharged to skilled nursing facilities (SNFs) after hospitalization, rates of patients recovery afterward are unknown.To examine postacute functional recovery among older adults.This cohort study was conducted among older adults treated in SNFs, then at home with home health care (HHC). Participants were a 5% random sample of Medicare fee-for-service beneficiaries discharged to community HHC after SNF stay from 2014 to 2016 with continuous part A and B enrollment in the prior 6 months. Medicare claims data from 2014 to 2016 were used, including inpatient, SNF, hospice, HHC, outpatient, carrier, and durable medical equipment data and Minimum Data Set (MDS) and Outcome Assessment Information Set (OASIS) for SNF and HHC assessments, respectively. Data were analyzed from July 20, 2020, to June 5, 2022.Frailty was measured with a validated claims-based frailty index (CFI) (range, 0-1; higher scores indicate worse frailty) and categorized into not frail (<0.20), mildly frail (0.20-0.29), and moderately to severely frail (≥0.30).The primary outcome was functional recovery, defined by discharge from HHC with stable or improved ability to perform activities of daily living (ADL). Recovery status was examined at 15, 30, 45, 60, 75, and 90 days after discharge to HHC using OASIS. Covariates were obtained from the MDS admission file at SNF admission, including age, race and ethnicity, cognitive status, functional status, and geographic region.Among 105 232 beneficiaries (mean [SD] age, 79.1 [10.6] years; 68 637 [65.2%] women; 8951 Black [8.5%], 3109 Hispanic [3.0%], and 88 583 White [84.2%] individuals), 65 796 individuals (62.5%) were discharged from HHC services with improved function over 90 days of follow-up. Among 39 436 beneficiaries not recovered, 19 612 individuals (49.7%) had mild frailty and 15 818 individuals (40.1%) had moderate to severe frailty. While 10 492 of 17 576 beneficiaries who were not frail recovered by 45 days (59.7%), 10 755 of 32 212 individuals with moderate to severe frailty had recovered (33.4%). Overall, frailty was negatively associated with functional recovery after adjustment for demographic characteristics, geographic census regions, and health-related variables, with a hazard ratio for moderate to severe frailty of 0.62 (95% CI, 0.60-0.63) compared with nonfrailty.This study found that recovery after posthospitalization SNF stay was particularly prolonged for individuals with frailty. Functional dependence in activities of daily living remained common among individuals with frailty long after discharge home.
Patient-Level and County-Level Trends in Nonfatal Opioid-Involved Overdose Emergency Medical Services Encounters — 491 Counties, United States, January 2018–March 2022
Authors: Shannon M. Casillas, Cassandra M. Pickens, Erin K. Stokes, Josh Walters, Alana Vivolo-Kantor
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The number of nonfatal opioid-involved overdoses treated by health care providers has risen in the United States; the median number of emergency department (ED) visits for these overdoses was significantly higher during 2020 than during 2019 (1). ED visit data can underestimate nonfatal opioid-involved overdose incidence because, increasingly, persons experiencing a nonfatal opioid overdose are refusing transport to EDs by emergency medical services (EMS) (2). A study in Kentucky found that during a 6-month period, 19.8% of persons treated by EMS for an opioid overdose refused transport to an ED (2). Thus, EMS encounter data involving suspected nonfatal opioid-involved overdoses complement ED data and also allow for near real-time analysis (3). This report describes trends in rates of EMS encounters for nonfatal opioid-involved overdoses per 10,000 total EMS encounters (rates) by selected patient- and county-level characteristics during January 2018–March 2022 in 491 counties from 21 states using data from biospatial, Inc.* During this period, the nonfatal opioid-involved overdose rate increased, on average, 4.0% quarterly. Rates increased for both sexes and for most age groups. Rates were highest among non-Hispanic White (White) and non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) persons, and increases were largest among non-Hispanic Black (Black), followed by Hispanic or Latino (Hispanic) persons. Rates increased in both urban and rural counties and for all quartiles of county-level characteristics (i.e., unemployment, education, and uninsured), except in counties with the lowest percentage of uninsured persons. Rates were highest and rate increases were largest in urban counties and counties with higher unemployment rates. This analysis of nonfatal opioid-involved overdose trends in EMS data highlights the utility of these data and the importance of addressing inequities that contribute to disproportionate overdose risk, such as through focused outreach to racial and ethnic minority groups, who disproportionately experience these inequities, and communities with higher levels of unemployment. EMS providers are in a unique position to engage in postoverdose response protocols and promote evidence-based overdose education and facilitate linkage to care and harm reduction services.†,§
Small Study Effects in Diagnostic Imaging Accuracy
Authors: Lucy Lu, Qi Sheng Phua, Stephen Bacchi, Rudy Goh, Aashray K. Gupta, Joshua G. Kovoor, Christopher D. Ovenden, Minh-Son To
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Small study effects are the phenomena that studies with smaller sample sizes tend to report larger and more favorable effect estimates than studies with larger sample sizes. <h3>Objective</h3> To evaluate the presence and extent of small study effects in diagnostic imaging accuracy meta-analyses. <h3>Data Sources</h3> A search was conducted in the PubMed database for diagnostic imaging accuracy meta-analyses published between 2010 and 2019. <h3>Study Selection</h3> Meta-analyses with 10 or more studies of medical imaging diagnostic accuracy, assessing a single imaging modality, and providing 2 × 2 contingency data were included. Studies that did not assess diagnostic accuracy of medical imaging techniques, compared 2 or more imaging modalities or different methods of 1 imaging modality, were cost analyses, used predictive or prognostic tests, did not provide individual patient data, or were network meta-analyses were excluded. <h3>Data Extraction and Synthesis</h3> Data extraction was performed in accordance with the PRISMA guidelines. <h3>Main Outcomes and Measures</h3> The diagnostic odds ratio (DOR) was calculated for each primary study using 2 × 2 contingency data. Regression analysis was used to examine the association between effect size estimate and precision across meta-analyses. <h3>Results</h3> A total of 31 meta-analyses involving 668 primary studies and 80 206 patients were included. Fixed effects analysis produced a regression coefficient for the natural log of DOR against the SE of the natural log of DOR of 2.19 (95% CI, 1.49-2.90; P &lt; .001), with computed tomography as the reference modality. Interaction test for modality and SE of the natural log of DOR did not depend on modality (Wald statistic<i>P</i> = .50). Taken together, this analysis found an inverse association between effect size estimate and precision that was independent of imaging modality. Of 26 meta-analyses that formally assessed for publication bias using funnel plots and statistical tests for funnel plot asymmetry, 21 found no evidence for such bias. <h3>Conclusions and Relevance</h3> This meta-analysis found evidence of widespread prevalence of small study effects in the diagnostic imaging accuracy literature. One likely contributor to the observed effects is publication bias, which can undermine the results of many meta-analyses. Conventional methods for detecting funnel plot asymmetry conducted by included studies appeared to underestimate the presence of small study effects. Further studies are required to elucidate the various factors that contribute to small study effects.
Association of headgear mandate and concussion injury rates in girls’ high school lacrosse
Authors: Daniel C Herman, Shane V Caswell, Patricia M Kelshaw, Heather K Vincent, Andrew E Lincoln
Journal: British Journal of Sports Medicine (2022)

Headgear use is a controversial issue in girls' lacrosse. We compared concussion rates among high school lacrosse players in an American state with a headgear mandate (HM) to states without an HM.Participants included high schools with girls' lacrosse programmes in the USA. Certified athletic trainers reported athlete exposure (AE) and injury data via the National Athletic Treatment, Injury and Outcomes Network during the 2019-2021 seasons. The HM cohort was inclusive of high schools from the state of Florida, which mandates the use of ASTM standard F3137 headgear, while the non-HM (NHM) cohort was inclusive of high schools in 31 states without a state-wide HM. Incidence rate ratios (IRRs) and 95% CIs were calculated.141 concussions (HM: 25; NHM: 116) and 357 225 AEs were reported (HM: 91 074 AEs; NHM: 266 151 AEs) across all games and practices for 289 total school seasons (HM: 96; NHM: 193). Overall, the concussion injury rate per 1000 AEs was higher in the NHM cohort (0.44) than the HM cohort (0.27) (IRR=1.59, 95% CI: 1.03 to 2.45). The IRR was higher for the NHM cohort during games (1.74, 95% CI: 1.00 to 3.02) but not for practices (1.42, 95% CI: 0.71 to 2.83).These findings suggest a statewide HM for high school girls' lacrosse is associated with a lower concussion rate than playing in a state without an HM. Statewide mandates requiring ASTM standard F3137 headgear should be considered to reduce the risk of concussion.
Navigating regulatory pathways for translation of biologic cartilage repair products
Authors: Rachel C. Nordberg, Gaston A. Otarola, Dean Wang, Jerry C. Hu, Kyriacos A. Athanasiou
Journal: Science Translational Medicine (2022)

Long-term clinical repair of articular cartilage remains elusive despite advances in cartilage tissue engineering. Only one cartilage repair therapy classified as a "cellular and gene therapy product" has obtained Food and Drug Administration (FDA) approval within the past decade although more than 200 large animal cartilage repair studies were published. Here, we identify the challenges impeding translation of strategies and technologies for cell-based cartilage repair, such as the disconnect between university funding and regulatory requirements. Understanding the barriers to translation and developing solutions to address them will be critical for advancing cell therapy products for cartilage repair to clinical use.
Modified endoscopic vacuum therapy for hypopharyngeal acute leakage after foreign body perforation
Authors: João Guilherme Ribeiro Jordão Sasso, Erika Yuki Yvamoto, Rodrigo Silva de Paula Rocha, Igor Braga Ribeiro, Mateus Bond Boghossian, Diogo Turiani Hourneaux de Moura, Eduardo Guimarães Hourneaux de Moura
Journal: Endoscopy (2022)

Conventional endoscopic vacuum therapy is currently used worldwide to treat esophageal leaks, with a healing rate of 67 %–100 % [1] [2]. The vacuum effect works through its effect on important mechanisms such as micro and macro deformation, tissue reperfusion, exudate control, and bacterial clearance [3]. Modified endoscopic vacuum therapy (MEVT) has some benefits when compared with the conventional technique, such as lower costs, less adherence, the requirement for fewer exchanges, and a shorter procedural duration [2]. In addition, it can be easily performed [4]. Although there were no reported cases of the use of hypopharyngeal vacuum therapy, we report a hypopharyngeal leak that was successfully treated with MEVT, leading to a new possibility when faced with hypopharyngeal defects.
Case 26-2022: A 48-Year-Old Woman with Cystic Lung Disease
Authors: Krishna P. Reddy, Melissa C. Price, Jeffrey A. Barnes, Nancy A. Rigotti, Rory K. Crotty
Journal: New England Journal of Medicine (2022)

A 48-year-old woman was evaluated for abdominal pain. CT showed numerous liver lesions and lung cysts and nodules; liver biopsy revealed an eosinophilic inflammatory infiltrate. A diagnosis was made.
Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis
Authors: Anna Marklund, Tobias Lekberg, Elham Hedayati, Annelie Liljegren, Jonas Bergh, Frida E. Lundberg, Kenny A. Rodriguez-Wallberg
Journal: JAMA Oncology (2022)

Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis.To investigate the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation compared with women who did not at time of BC diagnosis.This Swedish nationwide prospective cohort study was conducted to assess the safety of hormonal and nonhormonal FP procedures indicated by BC in Sweden from January 1, 1994, through June 30, 2017. Women were identified from any of the regional FP programs located at Swedish university hospitals. A total of 425 women were found to have undergone FP, and 850 population comparators who had not undergone FP were sampled from regional BC registers and matched on age, calendar period of diagnosis, and region. Relapse-free survival was assessed in a subcohort of 241 women who underwent FP and 482 women who had not, with complete data. Nationwide demographic and health care registers provided data on outcome, disease- and treatment-related variables, and socioeconomic characteristics. Data analyses were performed between November 2021 and March 2022 and completed in June 2022.Relapse and disease-specific mortality after a diagnosis of BC.The final study population included 1275 women (mean [SD] age, 32.9 [3.8] years) at the time of BC diagnosis. After stratification by the matching variables age, calendar period, and region, and adjustment for country of birth, education, parity at diagnosis, tumor size, number of lymph node metastases, and estrogen receptor status, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.32-1.09), women who underwent nonhormonal FP (aHR, 0.51; 95% CI, 0.20-1.29), and women who were not exposed to FP (reference). In a subcohort with detailed data on relapse, adjusted rate of disease-specific mortality and relapse were also similar among the groups who underwent hormonal FP (aHR, 0.81; 95% CI, 0.49-1.37), underwent nonhormonal FP (aHR, 0.75; 95% CI, 0.35-1.62), and were not exposed to FP (reference).In this cohort study, FP with or without hormonal stimulation was not associated with any increased risk of relapse or disease-specific mortality in women with BC. Results of this study provide much needed additional evidence on the safety of FP procedures in women with BC and may influence current health care practice to the benefit of young women with BC who wish to preserve their fertility.
Association of PD-L1 Expression and Other Variables With Benefit From Immune Checkpoint Inhibition in Advanced Gastroesophageal Cancer
Authors: Harry H. Yoon, Zhaohui Jin, Oudom Kour, Lionel Aurelien Kankeu Fonkoua, Kohei Shitara, Michael K. Gibson, Larry J. Prokop, Markus Moehler, Yoon-Koo Kang, Qian Shi, Jaffer A. Ajani
Journal: JAMA Oncology (2022)

Approval by the US Food and Drug Administration of immune checkpoint inhibition (ICI) for advanced gastroesophageal cancer (aGEC) irrespective of PD-L1 status has generated controversy. Exploratory analyses from individual trials indicate a lack of meaningful benefit from ICI in patients with absent or low PD-L1 expression; however, analysis of a single variable while ignoring others may not consider the instability inherent in exploratory analyses.
CDK8 and CDK19 regulate intestinal differentiation and homeostasis via the chromatin remodeling complex SWI/SNF
Authors: Marius V. Dannappel, Danxi Zhu, Xin Sun, Hui Kheng Chua, Marle Poppelaars, Monica Suehiro, Subash Khadka, Terry C.C. Lim Kam Sian, Dhanya Sooraj, Melissa Loi, Hugh Gao, Daniel Croagh, Roger J. Daly, Pouya Faridi, Thomas G. Boyer, Ron Firestein
Journal: Journal of Clinical Investigation (2022)

Initiation and maintenance of transcriptional states are critical for controlling normal tissue homeostasis and differentiation. The cyclin dependent kinases CDK8 and CDK19 (Mediator kinases) are regulatory components of Mediator, a highly conserved complex that orchestrates enhancer-mediated transcriptional output. While Mediator kinases have been implicated in the transcription of genes necessary for development and growth, its function in mammals has not been well defined. Using genetically defined models and pharmacological inhibitors, we showed that CDK8 and CDK19 function in a redundant manner to regulate intestinal lineage specification in humans and mice. The Mediator kinase module bound and phosphorylated key components of the chromatin remodeling complex switch/sucrose non-fermentable (SWI/SNF) in intestinal epithelial cells. Concomitantly, SWI/SNF and MED12-Mediator colocalized at distinct lineage-specifying enhancers in a CDK8/19–dependent manner. Thus, these studies reveal a transcriptional mechanism of intestinal cell specification, coordinated by the interaction between the chromatin remodeling complex SWI/SNF and Mediator kinase.